The mitochondria-related gene risk mode revealed p66Shc as a prognostic mitochondria-related gene of glioblastoma.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Glioblastoma*/genetics ; Glioblastoma*/metabolism ; Glioblastoma*/pathology ; Src Homology 2 Domain-Containing, Transforming Protein 1*/metabolism ; Src Homology 2 Domain-Containing, Transforming Protein 1*/genetics ; Mitochondria*/metabolism ; Mitochondria*/genetics ; Cell Proliferation* ; Gene Expression Regulation, Neoplastic*; Humans ; Prognosis ; Cell Line, Tumor ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Reactive Oxygen Species/metabolism ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Cell Movement/genetics ; Apoptosis/genetics ; Genes, Mitochondrial ; Female ; Male

Numerous studies have highlighted the pivotal role of mitochondria-related genes (MRGs) in the initiation and progression of glioblastoma (GBM). However, the specific contributions of MRGs coding proteins to GBM pathology remain incompletely elucidated. The identification of prognostic MRGs in GBM holds promise for the development of personalized targeted therapies and the enhancement of patient prognosis. We combined differential expression with univariate Cox regression analysis to screen prognosis-associated MRGs in GBM. Based on the nine MRGs, the hazard ratio model was conducted using a multivariate Cox regression algorithm. SHC-related survival, pathway, and immune analyses in GBM cohorts were obtained from the Biomarker Exploration of the Solid Tumor database. The proliferation and migration of U87 cells were measured by CCK-8 and transwell assay. Apoptosis in U87 cells was evaluated using flow cytometry. Confocal microscopy was employed to measure mitochondrial reactive oxygen species (ROS) levels and morphology. The expression levels of SHC1 and other relevant proteins were examined via western blotting. We screened 15 prognosis-associated MRGs and constructed a 9 MRGs-based model. Validation of the model's risk score confirmed its efficacy in predicting the prognosis of patients with GBM. Furthermore, analysis revealed that SHC1, a constituent MRG of the prognostic model, was upregulated and implicated in the progression, migration, and immune infiltration of GBM. In vitro experiments elucidated that p66Shc, the longest isoform of SHC1, modulates mitochondrial ROS production and morphology, consequently promoting the proliferation and migration of U87 cells. The 9 MRGs-based prognostic model could predict the prognosis of GBM. SHC1 was upregulated and correlated with the prognosis of patients by involvement in immune infiltration. Furthermore, in vitro experiments demonstrated that p66Shc promotes U87 cell proliferation and migration by mediating mitochondrial ROS production. Thus, p66Shc may serve as a promising biomarker and therapeutic target for GBM.
(© 2024. The Author(s).)

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81801908 The National Nature Science Foundation of China; 2022JJ70163 Hunan Provincial Natural Science Committee Project

Keywords: Glioblastoma; Immune infiltration; Mitochondria; ROS; p66Shc

0 (SHC1 protein, human)

Date Created: 20240519 Date Completed: 20240519 Latest Revision: 20240604

20240605

PMC11102912

10.1038/s41598-024-62083-2

38763954